Strong Impact of TGF-beta 1 Gene Polymorphisms on Breast Cancer Risk in Indian Women: A Case-Control and Population-Based Study

作者：Pooja Singh; Francis Amirtharaj; Rajender Singh; Tamang Rakesh; Rajkumar Raja; Saini Karan Singh; Megu Kaling; Goel Madhu Mati; Surekha Daminani; Rao Digumarthi Raghunatha; Rao Lakshmi; Ramachandra Lingadakai; Kumar Sandeep; Kumar Surender; Vishnupriya Satti; Satyamoorthy Kapaettu; Negi Mahendra Pal Singh; Thangaraj Kumarasamy^*; Konwar Rituraj

来源：PLos One, 2013, 8(10): e75979.

DOI：10.1371/journal.pone.0075979

Introduction: TGF-beta 1 is a multi-functional cytokine that plays an important role in breast carcinogenesis. Critical role of TGF-beta 1 signaling in breast cancer progression is well documented. Some TGF-beta 1 polymorphisms influence its expression; however, their impact on breast cancer risk is not clear.
Methods: We analyzed 1222 samples in a candidate gene-based genetic association study on two distantly located and ethnically divergent case-control groups of Indian women, followed by a population-based genetic epidemiology study analyzing these polymorphisms in other Indian populations. The c.29C>T (Pro10Leu, rs1982073 or rs1800470) and c.74G>C (Arg25Pro, rs1800471) polymorphisms in the TGF-beta 1 gene were analyzed using direct DNA sequencing, and peripheral level of TGF-beta 1 were measured by ELISA.
Results: c.29C>T substitution increased breast cancer risk, irrespective of ethnicity and menopausal status. On the other hand, c.74G>C substitution reduced breast cancer risk significantly in the north Indian group (p=0.0005) and only in the pre-menopausal women. The protective effect of c.74G>C polymorphism may be ethnicity-specific, as no association was seen in south Indian group. The polymorphic status of c.29C>T was comparable among Indo-Europeans, Dravidians, and Tibeto-Burmans. Interestingly, we found that Tibeto-Burmans lack polymorphism at c.74G>C locus as true for the Chinese populations. However, the Brahmins of Nepal (Indo-Europeans) showed polymorphism in 2.08% of alleles. Mean TGF-beta 1 was significantly elevated in patients in comparison to controls (p<0.001).
Conclusion: c.29C>T and c.74G>C polymorphisms in the TGF-beta 1 gene significantly affect breast cancer risk, which correlates with elevated TGF-beta 1 level in the patients. The c.29C>T locus is polymorphic across ethnically different populations, but c.74G>C locus is monomorphic in Tibeto-Burmans and polymorphic in other Indian populations.

• 出版日期2013-10-17
• 单位河北医科大学